Teratogen Flashcards
What percentage of live births have major birth defects?
3 - 4%
When do chromosomal abnormalities take place?
Chromosomal abnormalities preclude conception.
When does microcephaly develop?
Can develop relatively late in pregnancy
When does cleft palate typically occur?
Occurs towards the end of the first trimester
When do neural tube defects typically occur?
Occur in earliest weeks of gestation
What does Sonic hedgehog do?
Mammalian morphogen, regulating organogenesis, including growth of digits, brain organisation, sex organ differentiation, and lots more.
Where is sonic hedgehog produced?
In the notocord by node cells.
What type of protein is Sonic hedgehog?
It is a signalling morphogen. Determines cell responses in development: Key role in regulating vertebral organogenesis, growth of digits on limbs and brain organisation.
What is the job of Shh?
Important in the adult
Controls division of adult stem cells
Implicated in cancer development
Role in energy metabolism
What happens when Shh is mutated?
Mutations in SHH gene cause holoprosencephaly due to loss of ventral midline (it is a lethal mutation)
No Shh = no transcription of hedgehog-responsive genes.
What is the role of BMP4?
Involved in limb development
Knock outs are embryonic lethal
Mutants fail to properly form the mesoderm
Which fingers are SHH dependent?
The thumb is not SHH dependent.
The 3 most medial fingers are SHH dependent.
What happened to rhesus monkeys given thalidomide on the 26th day of pregnancy?
Abnormalities in forelimb, lower jaw, ear, and tail in 100 day rhesus monkey foetus.
How do teratogens affect birth defects?
Teratogens do not uniformly increase rates of all birth defects. They instead increase rates of specific defects:
Thalidomide affects limbs
Isotretinoin affects ear, CNS, and heart
Valproic acid affects neural tube etc
How does timing of teratogen affect what body system is hurt?
Each stage affects a specific system. Early stage affects CNS, Heart, and upper limbs.
